Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer

Sponsor

RenJi Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT02942563

Collaborator

(none)

100

Enrollment

Location

Arm

70.9

Anticipated Duration (Months)

1.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The concurrent neoadjuvant chemoradiation therapy is standard care for local advanced rectal cancer (LARC), however, this regimen may induce sorts of adverse events, and part of them even more severer. A number of pilot studies had shown high rate of complete resection after neoadjuvant chemotherapy alone, but the results did not increase the ratio of pathological complete response (pCR), which was associated with overall survival (OS). Here, the investigators adopt the three active cytotoxic agents (Fluorouracil, Oxaliplatin, Irinotecan, FOLFOXIRI) as the neoadjuvant chemotherapy regimen to replace the concurrent chemoradiation and to improve the ratio of pCR further.

Condition or Disease	Intervention/Treatment	Phase
Rectal Cancer	Drug: FOLFOXIRI	Phase 2

Detailed Description

This is a multicenter, phase II trial to assess the efficacy/safety of triplet regimen (FOLFOXIRI) for patients with LARC. After 4 cycles of FOLFOXIRI and 2 weeks later, the patients will be evaluated by senior radiologist, oncologist and surgeon through pelvic MRI, CT and Positron Emission Computed Tomography (PET-CT). The patients will go to surgery (TME) if the tumor response is good enough to have complete resection under the decision of MDT,otherwise, the patients will receive pelvic radiotherapy(45Grey/25Fraction and 5.4Grey/3Fraction boost to the tumor bed) combined with capecitabine(625mg/M^2, bid po, d1-5, qw), and additional four cycles of modified FOLFOX6 (mFOLFOX6) or Oxaliplatin 135mg/m²plus Capecitabine 1.0/m² bid po(XELOX) of each 3 weeks cycle for 2 cycles chemotherapy before TME. All patients will receive 6-8 cycles of mFOLFOX6 or 4-5 cycles XELOX as adjuvant chemotherapy after TME.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase II Study of Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer

Actual Study Start Date :

Nov 1, 2016

Anticipated Primary Completion Date :

Sep 30, 2019

Anticipated Study Completion Date :

Sep 30, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: FOLFOXIRI irinotecan* 165 mg/m² + oxaliplatin 85 mg/m² + leucovorin 200 mg/m² + 5-FU 2800 mg/m² cont. inf. 46h all on day 1 of each 2 weeks cycle	Drug: FOLFOXIRI Irinotecan* 165 mg/m² + oxaliplatin 85 mg/m² + leucovorin 200 mg/m² + 5-FU 2800 mg/m² cont. inf. 46h all on day 1 of each 2 weeks cycle for 4-6 cycles, Chemoradiation for patients who are not suitable to surgery: Pelvic radiotherapy(45Grey/25Fraction and 5.4Grey/3Fraction boost to the tumor bed) combined with capecitabine(625mg/m², bid po, d1-5, qw), and additional four cycles of modified FOLFOX6 (mFOLFOX6) or Oxaliplatin 135mg/m²plus Capecitabine 1.0/m² bid po(XELOX) of each 3 weeks cycle for 2 cycles chemotherapy before TME. All patients will receive 6-8 cycles of mFOLFOX6 or 4-5 cycles XELOX as adjuvant chemotherapy after TME. Other Names: Irinotecan Oxaliplatin 5-FU Capecitabine

Arm

Intervention/Treatment

Experimental: FOLFOXIRI

irinotecan* 165 mg/m² + oxaliplatin 85 mg/m² + leucovorin 200 mg/m² + 5-FU 2800 mg/m² cont. inf. 46h all on day 1 of each 2 weeks cycle

Drug: FOLFOXIRI

Irinotecan* 165 mg/m² + oxaliplatin 85 mg/m² + leucovorin 200 mg/m² + 5-FU 2800 mg/m² cont. inf. 46h all on day 1 of each 2 weeks cycle for 4-6 cycles, Chemoradiation for patients who are not suitable to surgery: Pelvic radiotherapy(45Grey/25Fraction and 5.4Grey/3Fraction boost to the tumor bed) combined with capecitabine(625mg/m², bid po, d1-5, qw), and additional four cycles of modified FOLFOX6 (mFOLFOX6) or Oxaliplatin 135mg/m²plus Capecitabine 1.0/m² bid po(XELOX) of each 3 weeks cycle for 2 cycles chemotherapy before TME. All patients will receive 6-8 cycles of mFOLFOX6 or 4-5 cycles XELOX as adjuvant chemotherapy after TME.

Other Names:

Irinotecan

Oxaliplatin

5-FU

Capecitabine

Outcome Measures

Primary Outcome Measures

Pelvic complete resection rate [Up to 10 weeks]
Pathologic confirmation

Secondary Outcome Measures

The rate of local control [3 years]
Imaging diagnosis
Disease free survival (DFS) [3 years]
Imaging diagnosis
Overall survival [3 years]
Record document
The rate of receive chemoradiation [Up to 10 weeks]
Record document
The rate of clinical complete response after 4 cycles of FOLFOXIRI [Up to 10 weeks]
Imaging diagnosis
The rate of pathological complete response after 4 cycles of FOLFOXIRI [Up to 10 weeks]
Pathologic confirmation
The incidence of >=3 grade adverse events [2 years]
Common Terminology Criteria for Adverse Events v3.0 (CTCAE)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age ≥ 18 to 75 years at diagnosis
Diagnosis of rectal adenocarcinoma
ECOG status: 0～1
Clinical stage II (T3-4, N0) or stage III (T1-4, N1-2)
Adequate bone marrow, hepatic and renal function as assessed by the following laboratory requirements conducted within 7 days of starting study treatment:
Leukocytes ≥ 4.0 x109/ L,
Absolute neutrophil count (ANC) ≥ 2.0 x109/ L
Platelet count ≥ 100 x109/ L,
Hemoglobin (Hb) ≥ 9g/ dL.
Total bilirubin ≤1.5 x the upper limit of normal (ULN).
Alanine aminotransferase (ALT) ≤ 3 x ULN
Aspartate aminotransferase (AST) ≤ 3 x ULN.
Serum creatinine ≤ 1.5 x the ULN.
Signed informed consent;